The purpose of this proposal is to provide a strong mentoring experience and didactic training to afford Dr. Beth Marshall the opportunity to attain her long term goal of becoming an independent investigator in an academic institution. To this end, we propose a multifaceted career development program consisting of: 1) didactic instruction via coursework and seminar attendance; 2) extensive mentoring in the form of 2 overseeing mentors and a 6-member Career Advisory Committee; 3) research training via a substantial and well-rounded clinical research project. The research we propose will test the hypothesis that pregnant women who have been infected with CMV one or more years prior to pregnancy (seropositive) are not completely protected against delivering congenially infected infants because they become reinfected with CMV just before or during pregnancy. Infection of the fetus with cytomegalovirus (CMV) results in approximately 8,000 infants born each year who will be mentally retarded and/or deaf. These effects are mainly due to primary maternal CMV infection during pregnancy. Although less common, seropositive women can also give birth to congenially infected infants, but what is not known is whether these women have sustained a reactivation of CMV or reinfection with another strain. The answer to this question has significant implications for both vaccine development as well as intervention strategies. To determine whether reinfection is the primary source of congenital infection in seropositive women, we will compare congenital infection rates in 3 groups of seropositive pregnant women: women with children shedding CMV, women without children shedding CMV, and women who have seroconverted just prior to pregnancy. Reinfection will be defined by demonstrating identical genomic patterns of virus shed by an older sibling (infected during the course of the study) and the newborn. Additionally, we will establish the immunologic responses and virologic aspects of those seropositive women who give birth to infected newborns, as this information is important for understanding the factors involved in the transmission of virus to the fetus, and ultimately for the development of an efficacious vaccine to prevent congenital CMV.